Gastric Endocrine Cells: Gene Expression, Processing, and Targeting of
Active Products.
Dockray, Graham J., Andrea Varro, and Rod Dimaline.
Physiological Laboratory, University of Liverpool, Liverpool, United
Kingdom.
APStracts 2:0013P, 1996.
ABSTRACT
Endocrine cells of the gastric epithelium secrete biologically active peptides
and small messenger molecules such as histamine, serotonin, and [gamma]-
aminobutyric acid. The secretory products may act locally (paracrine or
autocrine effects) or at distant targets after delivery in the circulation
(hormonal effects). The contents of the gastric lumen control both secretion
by gastric endocrine cells and the expression of genes involved in the
synthesis of their active secretory products; in some cases, gene regulation
may occur over periods as short as that required for digestion of a single
meal. The conversion of inactive peptide precursors to their active forms
takes place during transit along the secretory pathway and is only completed
after sequestration in secretory granules. The processing of the gastrin
precursor provides a useful model for studying prohormone processing.
Generation of the well-known amidated gastrins requires prohormone cleavage
and COOH-terminal amidation; the products stimulate acid secretion and mucosal
growth. However, recent work indicates that biosynthetic intermediates that do
not stimulate acid secretion may nevertheless act at a novel receptor to
stimulate growth, so that control of prohormone processing determines which of
two alternative types of biologically active peptide are released by gastrin
cells. Gastric endocrine cells also have the capacity to accumulate small
messenger molecules in secretory vesicles, via proton exchangers. Recent work
indicates physiological regulation of the expression of genes encoding
cytosolic enzymes such as histidine decarboxylase, which converts histidine to
histamine, and of secretory granule transporters such as vesicular monoamine
transporter type 2, which concentrates amines in secretory vesicles. Together
these findings suggest that modulation of regulatory peptide and amine
biosynthesis in gastric endocrine cells constitutes a primary response of the
stomach to the arrival of a meal
APS Manuscript Number P9-6.
Article publication pending July 1996, Physiological Reviews.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 4 July 96